Regulation of nucleotide synthesis will be investigated in detail for normal and experimental tumor tissues. The factors involved in specific enzyme systems concerned with purine nucleotide formation will be studied in vitro to determine how tissues like liver and bone marrow control their purine nucleotide concentrations at the molecular level, even under widely fluctuating metabolic demands. The mechanism of regulatory control of granulopoiesis will also receive special attention at the cellular and subcellular levels to define more precisely the specific macromolecular events involved in cellular proliferation and differentiation of normal and leukemic cell counterparts. Chemotherapeutic drugs of known efficacy will be employed both in vivo and in vitro to perturb these cell compartment types, and correlative clinical responses in man will be obtained.